Bernard H. Doft

Spectrum and Susceptibilities of Microbiologic Isolates in the Endophthalmitis Vitrectomy Study

PURPOSE To determine the microbiologic spectrum and antibiotic susceptibilities of infecting organisms in postoperative endophthalmitis and to evaluate the effects of operative factors on the microbiologic spectrum. METHODS Patients with bacterial endophthalmitis presenting within six weeks of cataract extraction or secondary intraocular lens implantation (IOL) were evaluated. Cultures and Gram stains were performed on intraocular specimens and susceptibility tests on the isolates. RESULTS Confirmed microbiologic growth was demonstrated from intraocular specimens from 291 of 420 patients (69.3%). Gram-positive bacteria were isolated from 274 patients (94.2%) with confirmed growth and gram-negative bacteria from 19 (6.5%). Two hundred twenty-six of the 323 isolates obtained (70.0%) were gram-positive, coagulase-negative micrococci, 32 (9.9%) Staphylococcus aureus, 29 (9.0%) Streptococcus species, seven (2.2%) Enterococcus species, ten (3.1%) miscellaneous gram-positive species, and 19 (5.9%) gram-negative species. All gram-positive isolates tested were susceptible to vancomycin. Seventeen gram-negative isolates (89%) were susceptible to both amikacin and ceftazidime and two (11%) were resistant to both. Anterior chamber or secondary IOL implantations were associated with higher rates of infection with gram-positives other than coagulase-negative micrococci than were posterior chamber IOL implantations (P = .022) or primary cataract extractions (P = .024). CONCLUSIONS Gram-positive, coagulase-negative micrococci predominated in this series. Vancomycin was active against all gram-positive isolates tested. Amikacin and ceftazidime showed equivalent activity against gram-negative isolates. Secondary or anterior chamber lens implantations were associated with a possible spectrum shift toward gram-positive organisms other than the coagulase-negative micrococci.

Contribution of Diabetes Duration Before Puberty to Development of Microvascular Complications in IDDM Subjects

The contribution of diabetes duration, both pre- and postpuberty, to the development of microvascular complications and mortality in diabetic subjects was investigated in three study populations from the Childrens Hospital of Pittsburgh Insulin-Dependent Diabetes Mellitus (IDDM) Registry. Life-table analyses by total and postpubertal IDDM duration were used to evaluate differences in the prevalence of microvascular complications and diabetes-related mortality in subjects diagnosed before and during puberty, as defined by an age at IDDM onset marker of 11 yr for girls and 12 yr for boys. The prevalence of retinopathy and overt nephropathy in 552 White adult diabetic subjects (population 1, mean IDDM duration 20.8 yr) was significantly greater in subjects diagnosed during puberty compared with those diagnosed before puberty. However, similar analyses by postpubertal duration showed no difference in microvascular complication prevalence between the two groups. These findings did not appear to be due to a confounding effect of age. Additional analyses of 239 adolescent diabetic subjects (population 2, mean duration 8.3 yr) revealed the same trend for the prevalence of retinopathy. Finally, results concerning the risk of diabetes-related mortality in a cohort of 1582 subjects (population 3, mean duration 12.9 yr) indicated that postpubertal duration of IDDM may be a more accurate determinant of the development of microvascular complications and diabetes-related mortality than total duration, and it is suggested that the contribution of the prepubertal years of diabetes to long-term prognosis may be minimal.

Single versus Multiple Treatment Sessions of Argon Laser Panretinal Photocoagulation for Proliferative Diabetic Retinopathy

A prospective, randomized study was performed to demonstrate whether there was a difference in the beneficial or adverse effects of argon laser photocoagulation for proliferative diabetic retinopathy depending on whether treatment was administered in a single session as compared with multiple sessions spaced over time. Results show no major differences between groups in the effect of treatment on visual acuity, visual field scores, or retinopathy risk factors. Exudative retinal detachment, choroidal detachment, and angle closure occurred more commonly in single session treatment group eyes, but these effects were transient, and no long-term difference between treatment groups was found.

Amphotericin Clearance in Vitrectomized Versus Nonvitrectomized Eyes

Ocular clearance of amphotericin B after direct intravitreal injection was studied in a rabbit model. Unmodified phakic eyes, Candida-infected eyes, aphakic eyes, and aphakic vitrectomized eyes were employed. Using high pressure liquid chromatography to assess drug level, the half-lives of drug disappearance after single 10-microgram (microgram) intravitreal injections were 9.1, 8.6, 4.7, and 1.4 days, respectively. The disappearance slope for vitrectomized eyes was significantly different from all nonvitrectomized eyes with P less than 0.001. The rapid disappearance of amphotericin from vitrectomized eyes must be considered in clinical management of patients with fungal endophthalmitis.

The Association Between Long-term Diabetic Control and Early Retinopathy

A study was performed to determine the relationship between level of long-term antecedent diabetic control and early diabetic retinopathy changes. Fifty-eight insulin dependent diabetics aged 14 to 17 1/2 years, with duration of diabetes of at least 8 years, were studied. Glycosylated hemoglobins were assessed a mean of 8.5 times per patient, over a mean period of 3.1 years, representing 28% of the mean duration of diabetes in this patient population. Fluorescein angiography, obtained according to a standardized technique, was assessed in masked fashion for number of microaneurysms, presence of abnormal areas of capillary nonperfusion, and presence of intraretinal dye leakage. Sixty-four percent of the study population showed some evidence of retinopathy. There was a high correlation found between degree of metabolic control as measured by glycosylated hemoglobin level, and presence of early retinopathy changes as defined by angiography.

Retinopathy Risk Factor Regression After Laser Panretinal Photocoagulation for Proliferative Diabetic Retinopathy

Fifty eyes of patients with proliferative diabetic retinopathy were followed at frequent intervals to determine the rapidity and stability of retinopathy risk factor regression after argon laser panretinal photocoagulation. Retinopathy risk factors regress rapidly after laser photocoagulation. The incidence of eyes at high risk for severe visual loss (eyes with 3 or more retinopathy risk factors) decreased from 100% prior to treatment to 28% three weeks after treatment. The early response to treatment was a good prognostic indicator of longer term results. Seventy-two percent of eyes which improved from a high- to a low-risk category by three weeks continued to remain at low risk at six months. Sixty-four percent of eyes which failed to improve to a low-risk category by three weeks continued to remain at high risk at six months. The early response to laser panretinal ablation may be used to predict longer-term results.

Additional procedures after the initial vitrectomy or tap-biopsy in the endophthalmitis vitrectomy study

OBJECTIVE The study aimed to assess the frequency, indications, and outcome of additional ocular procedures after initial treatment of vitrectomy (VIT) or tap-biopsy (TAP) for patients with endophthalmitis after cataract extraction. DESIGN The study design was an analysis of observational data collected as part of a multicenter, randomized clinical trial. PARTICIPANTS Of the 420 patients enrolled in the Endophthalmitis Vitrectomy Study, the 148 who had additional procedures were compared with the 272 who did not. MAIN OUTCOME MEASURES The types, indications, and number of additional ocular procedures were assessed. A masked examiner measured visual acuity 9 to 12 months after study entry. RESULTS Within 1 week of study entry, 8% of VIT eyes and 13% of TAP eyes underwent additional procedures, 14% for complications of the initial procedure and 86% for worsening ocular inflammation or infection. Cultures were obtained in 33 of the 38 eyes operated on for worsening inflammation or infection and were positive in 42%. Cultures obtained from the early additional procedures were positive more frequently in eyes with an initial TAP (71%) than in eyes with an initial VIT (13%). Both virulence of initial microbiologic organism isolated and poor presenting vision were risk factors for requirement of reoperation. In all cases in which a single organism was cultured at the initial procedure, when the reculture was positive, it was the same organism. Late additional procedures (after 7 days) were required in 27% of patients. Visual outcome was much worse for eyes that had an additional procedure compared to eyes that did not, and this was especially the case for eyes that had an early additional procedure. Only 15% of eyes that had an early additional procedure achieved 20/40 visual acuity as compared to 57% of eyes that did not. CONCLUSION Need for an additional procedure was a marker of more severe disease, and patients who underwent additional procedures achieved poorer visual acuity at final follow-up.

Diabetes Complications and Glycemk Control: The Pittsburgh Prospective Insulin-Dependent Diabetes Cohort Study Status Report After 5 yr of IDDM

The relationship between glycemic control and complications of insulin-dependent diabetes mellitus (IDDM) remains controversial. With the use of glycosylated hemoglobin (HbA,) to assess glycemic control from diagnosis onward, the Pittsburgh Prospective Insulin-Dependent Diabetes Mellitus Cohort Study prospectively evaluated 80 new cases of IDDM diagnosed at Childrens Hospital of Pittsburgh. This study presents findings in 62 patients at 5 yr postdiagnosis. Only 7 patients, all girls, had any retinopathy (microaneurysms). These subjects had an elevated 5-yr mean HbA1 compared to those with no retinopathy (13.0 vs. 11.7%; P < .05). Six female subjects who had an elevated albumin excretion rate (AER; >20 μg/min) had a higher 5-yr mean HbA, (13.3%) than the 26 subjects with AER <20 |xg/min (11.8%; P < .05). Current HbA1 was correlated with AER (r = +.36, P < .05) and systolic blood pressure (r = +.49, P < .01) in females. However, these associations were not observed in males. Positive correlations were found between HbA1 (5-yr mean and current) and serum triglyceride and cholesterol, but only in females was HbA1 inversely related to high-density lipoprotein cholesterol. However, HbA1 was independent of sex, HLA-DR type, and urine C-peptide status. Age adjustment did not change the above results. These analyses suggest that glycemic control is related to AER, systolic blood pressure, presence of microaneurysms, and serum triglyceride and cholesterol concentrations during the first 5 yr of IDDM. However, these associations appear to be predominant in girls.

Clinical predictors and outcomes of pars plana vitrectomy for retained lens material after cataract extraction.

PURPOSE To determine current clinical predictors and visual outcomes of patients who undergo pars plana vitrectomy (PPV) for retained lens material. DESIGN Retrospective, noncomparative, consecutive case series. METHODS Medical records of 166 patients with complicated cataract surgery who underwent PPV for retained lens material at Retina Vitreous Consultants of Pittsburgh between January 1, 2001 and January 1, 2007 were reviewed. Main outcome measures include final visual acuity, development of glaucoma, retinal detachments, and cystoid macular edema. RESULTS At the final examination, 120 patients (72.3%) had a visual outcome of 20/40 or better and 18 patients (10.8%) had a visual outcome of 20/200 or worse. In patients without any preoperative eye conditions, 82.6% achieved a final vision of 20/40 or better. Multivariable analysis showed that predictors for visual outcomes of 20/40 or better were better presenting vision (P = .001), insertion of a posterior chamber lens (P = .005), and absence of preoperative eye disease (P = .001). Predictors for visual outcomes of 20/200 or worse were the absence of an anterior vitrectomy at cataract surgery (P = .005), absence of a sulcus lens (P = .011), presence of preexisting eye disease (P = .02), and development of glaucoma (P = .001). Performing a PPV within 7 days of cataract surgery was associated with a lower risk of developing glaucoma (P = .005). CONCLUSIONS Current techniques for management of retained lens material may contribute to improved visual outcomes based on our series. We recommend that the cataract surgeon perform an anterior vitrectomy, place a posterior chamber lens if possible, and consult a retina specialist for a PPV within 7 days to decrease the risk of developing secondary glaucoma.

Postinjection Endophthalmitis in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT)

OBJECTIVE To describe the incidence and outcomes of endophthalmitis after intravitreal injections of anti-vascular endothelial growth factor agents in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) and to assess the effect of prophylactic topical antimicrobials on incidence. DESIGN Cohort study within a randomized clinical trial. PARTICIPANTS Patients enrolled in CATT. METHODS Patients with neovascular age-related macular degeneration received intravitreal injections of ranibizumab or bevacizumab under 1 of 3 dosing regimens. The study protocol specified preinjection preparation to include use of a sterile lid speculum and povidone iodine (5%). Use of preinjection and postinjection antibiotics was at the discretion of the treating ophthalmologist. Patients were followed up monthly for 2 years. MAIN OUTCOME MEASURES Development of endophthalmitis and visual acuity. RESULTS Endophthalmitis developed after 11 of 18 509 injections (1 per 1700 [0.06%]; 95% confidence interval, 0.03%-0.11%), and in 11 of 1185 patients (0.93%; 95% confidence interval, 0.52-1.66). Incidence of endophthalmitis was 0.15% among injections with no antibiotic use, 0.08% among injections with preinjection antibiotics only, 0.06% among injections with postinjection antibiotics only, and 0.04% among injections with preinjection and postinjection antibiotics (P = 0.20). All eyes were treated with intravitreal antibiotics and 4 underwent vitrectomy. Among the 11 affected eyes, the final study visual acuity was 20/40 or better in 4 eyes (36%), 20/50 to 20/80 in 2 eyes (18%), 20/100 to 20/160 in 3 eyes (27%), and worse than 20/800 in 2 eyes (18%). The final visual acuity was within 2 lines of the visual acuity before endophthalmitis in 5 eyes (45%). CONCLUSIONS Rates of endophthalmitis were low and similar to those in other large-scale studies. Use of topical antibiotics either before or after injection does not seem to reduce the risk for endophthalmitis.